Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update

Craig R Lee¹, Jasmine A Luzum², Katrin Sangkuhl³, Roseann S Gammal^{4

5}, Marc S Sabatine⁶, Charles Michael Stein⁷, David F Kisor⁸, Nita A Limdi⁹, Yee Ming Lee¹⁰, Stuart A Scott^{11

12}, Jean-Sébastien Hulot¹³, Dan M Roden¹⁴, Andrea Gaedigk¹⁵, Kelly E Caudle⁵, Teri E Klein³, Julie A Johnson¹⁶, Alan R Shuldiner¹⁷

Affiliations

¹ Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA.
² Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
³ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
⁴ Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA.
⁵ Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁶ Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
⁸ Department of Pharmaceutical Sciences, Manchester University, Fort Wayne, Indiana, USA.
⁹ Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁰ Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
¹¹ Department of Pathology, Stanford University, Stanford, California, USA.
¹² Clinical Genomics Laboratory, Stanford Health Care, Palo Alto, California, USA.
¹³ Université de Paris, CIC1418 and DMU CARTE, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.
¹⁴ Departments of Medicine and Pharmacology, Office of Personalized Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
¹⁵ Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City and University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USA.
¹⁶ Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
¹⁷ Department of Medicine, and Program for Genomic and Personalized Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.

PMID: 35034351
PMCID: PMC9287492
DOI: 10.1002/cpt.2526

Practice Guideline

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update

Craig R Lee et al. Clin Pharmacol Ther. 2022 Nov.

. 2022 Nov;112(5):959-967.

doi: 10.1002/cpt.2526. Epub 2022 Feb 8.

Authors

Affiliations

¹ Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA.
² Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
³ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
⁴ Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA.
⁵ Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁶ Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
⁸ Department of Pharmaceutical Sciences, Manchester University, Fort Wayne, Indiana, USA.
⁹ Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁰ Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
¹¹ Department of Pathology, Stanford University, Stanford, California, USA.
¹² Clinical Genomics Laboratory, Stanford Health Care, Palo Alto, California, USA.
¹³ Université de Paris, CIC1418 and DMU CARTE, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.
¹⁴ Departments of Medicine and Pharmacology, Office of Personalized Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
¹⁵ Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City and University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USA.
¹⁶ Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
¹⁷ Department of Medicine, and Program for Genomic and Personalized Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.

PMID: 35034351
PMCID: PMC9287492
DOI: 10.1002/cpt.2526

Abstract

CYP2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 genotype impacts clopidogrel active metabolite formation. CYP2C19 intermediate and poor metabolizers who receive clopidogrel experience reduced platelet inhibition and increased risk for major adverse cardiovascular and cerebrovascular events. This guideline is an update to the 2013 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of clopidogrel based on CYP2C19 genotype and includes expanded indications for CYP2C19 genotype-guided antiplatelet therapy, increased strength of recommendation for CYP2C19 intermediate metabolizers, updated CYP2C19 genotype to phenotype translation, and evidence from an expanded literature review (updates at www.cpicpgx.org).

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Conflict of interest statement

Conflicts of Interest:

In addition to his part-time faculty appointment at the University of Maryland School of Medicine, A.R.S. is an employee of Regeneron Pharmaceuticals, Inc and receives stock options and restricted stock units as part of his compensation. S.A.S. is a paid consultant of Sema4. J.S.H. has received speaker, advisory board or consultancy fees from Amgen, Astra Zeneca, Bayer, Bioserenity, Bristol-Myers Squibb, MSD, Novartis, Vifor, all unrelated to the present guidelines. M.S.S. reports grants and personal fees from Amgen, Anthos Therapeutics, AstraZeneca, Intarcia, Medicines Company, MedImmune, and Merck; personal fees from Althera, Bristol-Myers Squibb, CVS Caremark, DalCor, Dr. Reddy’s Laboratories, Dyrnamix, Fibrogen, IFM Therapeutics, and Novo Nordisk; and grants from Bayer, Daiichi-Sankyo, Eisai, IONIS, Novartis, Pfizer and Quark Pharmaceuticals, and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from: Abbott, Regeneron, Roche, and Zora Biosciences. All other authors declared no competing interests for this work.

References

1. Scott SA et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clinical pharmacology and therapeutics 94, 317–23 (2013). - PMC - PubMed
1. Cavallari LH et al. Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. JACC Cardiovasc Interv 11, 181–91 (2018). - PMC - PubMed
1. Claassens DMF et al. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N Engl J Med 381, 1621–31 (2019). - PubMed
1. Pereira NL et al. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA 324, 761–71 (2020). - PMC - PubMed
1. Pereira NL et al. Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis. JACC Cardiovasc Interv 14, 739–750 (2021). - PMC - PubMed

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Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update

Affiliations

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical